Blood sugar

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

Blood sugar is a term used to refer to the amount of glucose in the blood. Glucose, transported via the bloodstream, is the primary source of energy for the body's cells.

Blood sugar concentration, or glucose level, is tightly regulated in the human body. Normally, the blood glucose level is maintained between about 4 and 8 mmol/L (70 to 150 mg/dL). The total amount of glucose in the circulating blood is therefore about 3.3 to 7g (assuming an ordinary adult blood volume of 5 liters). Glucose levels rise after meals and are usually lowest in the morning, before the first meal of the day.

Failure to maintain blood glucose in the normal range leads to conditions of persistently high (hyperglycemia) or low (hypoglycemia) blood sugar. Diabetes mellitus, characterized by persistent hyperglycemia of several causes, is the most prominent disease related to failure of blood sugar regulation.

Though it is called "blood sugar" and sugars besides glucose are found in the blood, like fructose and galactose, only glucose levels are regulated via insulin and glucagon.

Glucose Measurement

Sample Type

Glucose can be measured in whole blood, serum, or plasma. Historically, blood glucose values were given in terms of whole blood, but most laboratories now measure and report the serum glucose levels. Because RBC (erythrocytes) have a higher concentration of protein (i.e. hemoglobin) than serum, serum has a higher water content and consequently more dissolved glucose than does whole blood. To convert from whole-blood glucose, multiply the value by 1.15 to give the serum/plasma level.

Collection of blood in clot (red-top) tubes for serum chemistry analysis permits the metabolism of glucose in the sample by blood cells until separated by centrifugation. Higher than normal amounts of white or red blood cell counts can lead to excessive glycolysis in the sample with substantial reduction of glucose level if the sample is not processed quickly. Ambient temperature at which the blood sample is kept prior to centrifugation and separation of Plasma/Serum also affects glucose levels. At refrigerator temperatures, glucose remains relatively stable for several hours in the blood sample. At room temperature (25°C), a loss of 1 to 2% of glucose per hour should be expected. The loss of glucose levels in aforementioned conditions can be prevented by using Fluoride top (gray-top) as the anticoagulant of choice upon blood collection, as Fluoride inhibits glycolysis. However, this should only be used when blood will be transported from one hospital laboratory to another for glucose measurement. Red-top serum separator tubes also preserve glucose in samples once they have been centrifugated to isolate the serum from cells, this tube would be the most efficient. Particular care should be given to drawing blood samples from the arm opposite the one in which an intravenous line is inserted, to prevent contamination of the sample with intravenous fluids (IV). Alternatively, blood can be drawn from the same arm with an IV line after the IV was turned off for at least 5 minutes and the arm is elevated to drain the infused fluids away from the vein. As little as 10% contamination with 5% dextrose (D5W) will elevate glucose in a sample by 500mg/dl or more. Arterial, capillary and venous blood have comparable glucose levels in a fasting individual, whereas after meals venous levels are lower than capillary or arterial blood.

Methodology

There are two different major methods that have been used to measure glucose. The older one is a chemical method that exploits the nonspecific reducing property of glucose in a reaction with an indicator substance that acquires or changes color on its reduction. Since other blood compounds also have reducing properties (e.g., urea, which can build up in uremic patients), this method can have erroneous measurements up to 5 to 15 mg/dl. This is solved by the Enzymatic methods that are highly specific for glucose. The two most common employed enzymes are glucose oxidase and hexokinase.

I. CHEMICAL METHODS
A. Oxidation-Reduction Reaction
<math>Glucose + Alkaline Copper Tartarate\xrightarrow{Reduction} Cuprous Oxide </math>
1. Alkaline Copper Reduction
Folin Wu Method	<math>Cu^{++} + Phosphomolybdic Acid\xrightarrow{Oxidation} Phosphomolybdenum Oxide</math>	Blue end-product
Benedict's method	Modification of Folin wu for Qualitative Urine Glucose
Nelson Somoygi Method	<math>Cu^{++} + Arsenomolybdic Acid\xrightarrow{Oxidation} Arsenomolybdenum Oxide</math>	Blue end-product
Neocuproine Method	<math>Cu^{++} + Neocuproine\xrightarrow{Oxidation} Cu^{++} Neocuproine Complex </math>*	Yellow-orange color Neocuproine
Shaeffer Hartmann Somygi	Utilizes the principle of Iodine reaction with Cuprous byproduct. Excess I2 is then titrated with thiosulfate.
2. Alkaline Ferricyanide Reduction
Hagedorn Jensen	<math>Glucose + Alk. Ferricyanide Yellow\longrightarrow Ferrocyanide</math>	Colorless end product; other reducing substances interfere with reaction
B. Condensation
Orht-touidine Method	Utilizes aromatic amines and hot acetic acid Forms Glycosylamine and Schiff's base which is emerald green in color This is the most specific method, but the reagent used is toxic
Anthrone (Phenols) Method	Forms hydroxymethyl furfural in hot acetic acid
II. ENZYMATIC METHODS
A. Glucose Oxidase
<math>Glucose + O^{2}\xrightarrow[Oxidation] {glucose oxidase}Cuprous Oxide </math>
Saifer Gernstenfield Method	<math>H_{2}O_2 + O-dianisidine\xrightarrow[Oxidation] {peroxidase} H_2O + oxidized chromogen</math>	Inhibited by reducing substances like BUA, Bilirubin, Glutathione, Ascorbic Acid
Trinder Method	uses 4-aminophenazone oxidatively coupled with Phenol Subject to less interference by increases serum levels of Creatinine, Uric Acid or Hemoglobin Inhibited by Catalase
Kodak Ektachem	A Dry Chemistry Method Uses Reflectance Spectrophotometry to measure the intensity of color through a lower transparent film
Glucometer	Home monitoring blood glucose assay method Uses a strip impregnated with a Glucose Oxidase reagent
B. Hexokinase
<math> \begin{alignat}{2} & Glucose + ATP\xrightarrow[Phosphorylation] {Hexokinase + Mg^{++}} G-6PO_4 + ADP \\ & G-6PO_4 + NADP\xrightarrow[Oxidation] {G-6PD} G-Phosphogluconate + NADPH + H^{+} \\ \end{alignat} </math>
NADP as cofactor NADPH (reduced product) is measured in 340 nm More specific than Glucose Oxidase method due to G-6PO_4, which inhibits interfering substances except when sample is hemolyzed

Laboratory Tests Commonly Employed

1. Fasting Blood Sugar or Glucose test (FBS)
2. Urine Glucose test
3. Two-hr Postprandial Blood Sugar Test (2-h PPBS)
4. Oral Glucose Tolerance test (OGTT)
5. Intravenous Glucose Tolerance test (IVGTT)
6. Glycosylated Hemoglobin (HbA_1C)
7. Self-monitoring of Glucose level via Home Kits

Clinical Correlation

The fasting blood glucose (FBG) level is the most commonly used indication of overall glucose homeostasis. Conditions that affect glucose levels are shown in the table below. They reflect abnormalities in the multiple control mechanism of glucose regulation.

The metabolic response to a carbohydrate challenge is conveniently assessed by the postprandial glucose level drawn 2 hours after a meal or a glucose load. In addition, the glucose tolerance test, consisting of serial timed measurements after a standardized amount of oral glucose intake, is used to aid in the diagnosis of Diabetes.

Causes of Abnormal Glucose Levels

Persistent Hyperglycemia	Transient Hyperglycemia	Persistent Hypoglycemia	Transient Hypoglycemia
Reference Range, FBG: 70-110 mg/dl
Diabetes Mellitus	Pheochromocytoma	Insulinoma	Acute Alcohol Ingestion
Adrenal cortical hyperactivity Cushing's Syndrome	Severe Liver Disease	Adrenal cortical insufficiency Addison's Disease	Drugs: salicylates, antituberculosis agents
Hyperthyroidism	Acute stress reaction	Hypopituitarism	Severe Liver disease
Acromegaly	Shock	Galactosemia	Several Glycogen storage diseases
Obesity	Convulsions	Ectopic Insulin production from tumors	Hereditary fructose intolerance

Health Effects

If blood sugar levels drop too low, a potentially fatal condition called hypoglycemia develops. Symptoms may include lethargy, impaired mental functioning, irritability, and loss of consciousness.

If levels remain too high, appetite is suppressed over the short term. Long-term hyperglycemia causes many of the long-term health problems associated with diabetes, including eye, kidney, and nerve damage.

Low Blood Sugar

Some people report drowsiness or impaired cognitive function several hours after meals, which they believe is related to a drop in blood sugar, or "low blood sugar". For more information, see:

• idiopathic postprandial syndrome
• hypoglycemia

Converting Glucose Units

Countries that use the metric system use mmol/L. The U.S. uses mg/dL.
To convert Blood Glucose readings:

• Divide the mg/dL by 18 to get mmol/L (or multiply by 0.055).
• Multiply the mmol/L by 18 to get mg/dL (or divide with 0.055).

References

• John Bernard Henry, M.D.: Clinical diagnosis and Management by Laboratory Methods 20th edition, Saunders, Philadelphia, PA, 2001.
• Ronald A. Sacher and Richard A. McPherson: Widmann's Clinical Interpretation of Laboratory Tests 11th edition, F.A. Davis Company, 2001.

External links

• Other medical conversions (Albumin, Protein, Creatinine, Creatinine clearance, Cholesterol, Lipid profile, Insulin, Etc..)
• Lab Tests Online: Glucose
• Alcohol and Blood Sugar

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